This invention relates to a pharmaceutical adhesive plaster composed of at least two parts joined together, of one part which contains the active ingredient and consists of a composite film with a shallow recess for containing the medicament. Optionally, it can have an innermost layer of a thermoplastic synthetic resin, in particular in the form of a film, and an outer layer of adhesive which is pressure-sensitive and/or sensitive to the heat of the skin (skin compatible) surrounding the recess in the form of a ring on the opening side of the recess. The other part consists of a composite film serving as a covering, optionally with an innermost layer of a thermosplastic synthetic resin, in particular in the form of a film, which covering is joined to the adhesive layer and covers the recess of the part containing the active ingredient; in other words, a so-called transdermal therapeutic system.
In a medicinal plaster of this kind disclosed in European publication No. 0 013 606 A 2, the medicament which contains or constitutes the active ingredient and diffuses into the skin is distributed in a so-called diffusion matrix embedded in the recess of the part for containing the active ingredient. The composite covering film of the known plaster is provided on its internal surface with a so-called separating layer which corresponds to the layer of adhesive and from which the layer of adhesive can easily be detached when the covering film is separated from the active ingredient container. The diffusion matrix is either inserted in the recess of the composite film containing the active ingredient or is poured into this recess and solidified therein.
One of the main disadvantages of this arrangement is that the so-called galenical, that is to say the preparation of active ingredient in the medicament, depends on the properties of the chosen matrix so that these properties must be taken into account, with the result that it is difficult to optimize the galenical.
It is therefore an object of the present invention to provide a pharmaceutical adhesive plaster in which this first disadvantage is overcome and which enables the galenical to be optimized independently of the properties of the matrix.
In a plaster of the type defined above, this problem is solved according to the invention by means of the fact that the recess of the active ingredient container is closed by a membrane which is permeable to the active ingredient and firmly connected to the composite film of the active ingredient container and that the composite film constituting the covering is hermetically connected to the composite film of the active ingredient container along a ring extending between the membrane and the layer of adhesive.
This has the advantageous result of providing a completely free choice of galenical for which a suitable membrane can be selected, this membrane serving to retain the medicament in the recess of the active ingredient container while enabling it to be gradually transmitted to the skin.
The known plaster, which is hermetically sealed in a flat bag until required for use, has the further disadvantage that the diffusion matrix is not capable of completely delivering to the skin all the medicament or active ingredient contained in it, especially that contained at the bottom of the recess because this portion must first itself diffuse through the matrix before it can diffuse into the skin in contact with the matrix. The dose provided by the container is therefore insufficient unless an appropriate excess of medicament has from the start been introduced into the matrix, but this procedure in some cases considerably increases the cost of production. The use of the known plaster may thus result in incorrect dosage of the medicament applied.
It is therefore a further object of the present invention to provide a pharmaceutical adhesive plaster which overcomes this disadvantage and results in virtually correct dosage due to almost complete exhaustion of the medicament. In a plaster of the type defined above, this problem is solved according to the invention by means of the fact that the recess of the active ingredient container only contains the medicament which constitutes or contains the active ingredient and which diffuses into the skin, this recess being most preferably closed by the membrane which is permeable to the active ingredient and firmly attached to the composite film of the active ingredient container. In this arrangement, the composite film forming the covering is hermetically attached to the composite film of the active ingredient container along the ring between the membrane and the layer of adhesive. The term "hermetic" is used to denote that no air can enter the interior of the plaster and no active ingredient can leave the interior.
The advantageous result is thereby achieved that the medicament, which can be constantly given off to the skin in small quantities while the mass of medicament is held back by the membrane, which is semi-permeable or may have been rendered diffusible, for example, by perforation, can be used up almost completely, no significant residues being left in the active ingredient container. This not only greatly facilitates accurate dosing of the medicament but also enables it to be carried out more economically since it is now not necessary to provide for an excess when a minimum dosage is required. Furthermore, it is now unnecessary to provide a separate envelope for the plaster since the parts of the plaster are not only glued together but also welded.
In DE-U- No. 84 24 387 (ALLPACK) it has already been proposed to solve the last mentioned problem in a pharmaceutical adhesive plaster of the type defined above by filling the recess of the active ingredient container only with the medicament containing or constituting the active ingredient which diffuses into the skin and covering the recess with a membrane which is permeable to the active ingredient and is firmly attached to the composite film of the active ingredient container, and by hermetically connecting the composite film of the covering to the composite film of the active ingredient container along a ring between the membrane and the layer of adhesive, the said covering film optionally lying with its flat surface in direct contact with the layer of adhesive. In that case, a preferred embodiment of the plaster according to the invention differs from the plaster previously proposed in that composite film forming the covering is indirectly in contact by its flat internal surface with the layer of adhesive which forms part of a third part of the plaster forming a ring round the recess containing active ingredient. This third component of the plaster is firmly connected both to the composite film of the active ingredient container and to the composite film of the covering and can be separated into two parts along the sticky side of the layer of adhesive facing the covering, this separation into two parts exposing the said adhesive surface.
By providing this third part of the plaster next to the membrane and in addition to the active ingredient container and the covering film, it is most easily possible to provide the most suitable material conditions for separating the covering from the ingredient container to expose the layer of adhesive and the membrane because the two components of the third part of the plaster, one of which carries the layer of adhesive and the other a counter-layer, may themselves be composed of a plurality of layers so that it is possible to choose the most suitable combination of materials for the pairs of layers to be joined together, including also at the boundaries between the third plaster part and the composite film of the active ingredient container and between the third plaster part and the covering film.